What is the diagnosis and management plan for a patient with cognitive decline, prosopagnosia, gait and balance disturbance, and mood changes suggestive of prominent frontal lobe dysfunction and temporal lobe involvement?

Diagnosis: Probable Alzheimer's Disease with Posterior Cortical Atrophy (Visuospatial Variant) or Mixed Alzheimer's Disease and Frontotemporal Pathology

Based on the clinical presentation of multi-domain cognitive decline with prominent prosopagnosia (impaired face recognition), visuospatial difficulties, executive dysfunction, gait disturbance, and mood changes, this patient most likely has Alzheimer's disease with a non-amnestic visuospatial presentation, though behavioral variant frontotemporal dementia (bvFTD) or mixed pathology must be considered in the differential diagnosis. 1

Diagnostic Formulation

Step 1: Establish Dementia Criteria

• Confirm cognitive impairment is interfering with independence in functional abilities through detailed history from both patient and informant, as impaired insight is common in neurodegenerative disorders 1, 2
• Document insidious onset over months to years (not sudden over hours or days) with clear-cut history of cognitive worsening 1
• Verify multi-domain involvement affecting memory, executive function, visuospatial abilities, and behavior 1

Step 2: Determine Clinical Syndrome

The visuospatial presentation with prosopagnosia strongly suggests AD with posterior cortical involvement, as the 2025 Alzheimer's Association guidelines specifically list "impaired face recognition" as a defining feature of the visuospatial presentation of probable AD dementia 1. However, the prominent frontal features (executive dysfunction, mood changes, gait disturbance) require careful consideration of alternative or mixed diagnoses.

Key Distinguishing Features:

For AD Visuospatial Variant:

• Prosopagnosia, object agnosia, simultanagnosia, and alexia are characteristic 1
• Medial temporal atrophy with paralimbic and temporoparietal cortical involvement on MRI 3
• Deficits in other cognitive domains must be present alongside visuospatial impairment 1

For Behavioral Variant FTD (if prominent):

• Social and emotional changes with disinhibition, apathy, lack of empathy predominate early 2, 4
• Frontal and/or anterior temporal atrophy on structural imaging 2, 4
• Critical exclusion criterion: The 2025 guidelines state that probable AD dementia should NOT be diagnosed when there are "prominent features of behavioral variant frontotemporal dementia" 1

For Mixed Pathology:

• Given the combination of posterior cortical features (prosopagnosia, visuospatial deficits) AND frontal features (executive dysfunction, mood changes), mixed AD and frontotemporal pathology is possible, particularly in patients over age 85 1

Step 3: Diagnostic Workup

Essential Neuroimaging:

Brain MRI without contrast is the preferred initial imaging modality 5:

• Look for medial temporal lobe atrophy (hippocampus, amygdala) with temporal horn enlargement, characteristic of AD 3
• Assess for posterior cortical atrophy in parietal and occipital regions, which would support visuospatial variant AD 5, 3
• Evaluate frontal lobe atrophy patterns - if prominent frontal/anterior temporal atrophy is present, this increases likelihood of bvFTD or mixed pathology 5, 2
• Rule out vascular disease - extensive white matter hyperintensities or multiple infarcts would suggest vascular contributions 1

Advanced Imaging (Second-Tier):

FDG-PET should be obtained if MRI findings are ambiguous 2:

• AD pattern: Hypometabolism in temporoparietal cortices and posterior cingulate, with relative preservation of sensorimotor cortex 1
• bvFTD pattern: Hypometabolism in prefrontal, frontal, and anterior temporal regions 5, 2
• Posterior cortical atrophy pattern: Occipital and parietal hypometabolism 1

Biomarker Testing (When Available):

Amyloid PET or CSF biomarkers (Aβ42, p-tau) should be pursued to increase diagnostic certainty 1:

• If both amyloid and tau biomarkers are positive: High likelihood dementia is due to AD 1
• If both are negative: Dementia is highly unlikely due to AD; consider FTLD or other etiologies 1
• If conflicting: Likelihood is intermediate; mixed pathology possible 1

Genetic testing for C9orf72, MAPT, and GRN mutations should be strongly considered, especially if family history is present or if bvFTD features are prominent 2, 4

Neuropsychological Testing:

• Formal assessment of visuospatial function to document prosopagnosia and other visual processing deficits 1
• Executive function testing (reasoning, judgment, problem-solving) to quantify frontal dysfunction 1
• Social cognition testing (Ekman 60 Faces Test, Theory of Mind tasks) if bvFTD is suspected 2
• Memory testing to determine if episodic memory is relatively preserved (more consistent with bvFTD) or impaired (more consistent with AD) 1, 2

Exclusion of Other Causes:

• Rule out Lewy body dementia: Assess for visual hallucinations, REM sleep behavior disorder, parkinsonism; consider dopamine transporter imaging (I-123 ioflupane SPECT) if clinical features are present 1
• Exclude vascular dementia: Document vascular risk factors, assess for temporal relationship between strokes and cognitive decline 1
• Screen for reversible causes: Thyroid function, B12, metabolic panel 1

Management Plan

Pharmacological Treatment

Cholinesterase inhibitors (rivastigmine, donepezil, or galantamine) should be initiated if AD is the likely diagnosis 5, 6:

• Rivastigmine has FDA approval for both AD and Parkinson's disease dementia, with demonstrated efficacy in improving ADAS-cog scores and global clinical impression 6
• Target dose for rivastigmine is 6-12 mg/day in divided doses, with gradual titration over 16 weeks to minimize gastrointestinal side effects 6
• Initiate early in the disease course for modest improvement or stabilization of cognitive symptoms 5

Memantine may be added for moderate-to-severe dementia if the patient progresses 1

Avoid cholinesterase inhibitors if bvFTD is the primary diagnosis, as evidence for efficacy is lacking and they may worsen behavioral symptoms 4

Non-Pharmacological Interventions

For visuospatial and executive deficits:

• Occupational therapy to develop compensatory strategies for daily activities and spatial navigation 5
• Environmental modifications to reduce visual complexity and support wayfinding 5
• Structured routines to compensate for executive dysfunction 2

For gait and balance disturbance:

• Physical therapy assessment is critical, as gait disorders in dementia are related to severity of cognitive decline and dual-task interference 7
• Fall prevention strategies, as dual-task disturbances are specific markers of falling risk in dementia 7
• Regular physical activity to potentially slow cognitive decline 5

For mood and behavioral changes:

• Antidepressants (SSRIs) for irritability and mood symptoms, particularly if bvFTD features are present 4
• Low-dose atypical antipsychotics (quetiapine, aripiprazole) may be considered for severe behavioral disturbance, but use cautiously due to increased mortality risk 4
• Behavioral interventions and caregiver education about redirecting attention and managing disinhibition 2

Disease Monitoring and Support

Regular follow-up every 3-6 months to monitor disease progression, as imaging findings typically worsen over time 5:

• Serial cognitive assessments to track decline in specific domains 1
• Functional status evaluation to adjust care plans as independence declines 1
• Reassess diagnosis if clinical course is atypical or non-progressive 2

Caregiver education and support:

• Educate about expected clinical course, including progression of visuospatial deficits, executive dysfunction, and potential behavioral changes 5, 2
• Provide information about support groups and respite care resources 1
• Discuss advance care planning early in the disease course, including goals of care, legal/financial planning, and end-of-life preferences 5

Critical Pitfalls to Avoid

• Do not assume this is typical amnestic AD - the prominent prosopagnosia and visuospatial deficits indicate a non-amnestic presentation that requires different diagnostic considerations 1
• Do not overlook mixed pathology, especially in older patients (>85 years), where AD commonly coexists with vascular disease, Lewy bodies, or FTLD pathology 1
• Do not diagnose bvFTD based solely on behavioral changes - executive dysfunction and mood changes can occur in AD, particularly with frontal involvement 1
• Do not miss Lewy body dementia - if visual hallucinations, parkinsonism, or REM sleep behavior disorder emerge, reconsider the diagnosis 1
• Do not delay biomarker testing when diagnosis is uncertain, as this directly impacts treatment eligibility for disease-modifying therapies 1
• Recognize that 10% of pathologically-confirmed bvFTD patients show marked episodic memory deficits at presentation, which can mimic AD 2